Water → tert-butyl 2-(2-(2H-1,2,3-triazol-2-yl)benzyl)-1-oxo-2,9-diazaspiro[5.5]-undecane-9-carboxylate

HRID 41576Notes

Reaction equation

HRID 41576 reaction equation
[H-].[Na+].[O:3]=[C:4]1[C:9]2([CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)[CH2:8][CH2:7][CH2:6][NH:5]1.Br[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[N:30]1[N:34]=[CH:33][CH:32]=[N:31]1.O>CCCC[N+](CCCC)(CCCC)CCCC.[I-].C1COCC1>[N:31]1[N:30]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[CH2:23][N:5]2[CH2:6][CH2:7][CH2:8][C:9]3([CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][CH2:14]3)[C:4]2=[O:3])[N:34]=[CH:33][CH:32]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 49760149tert-Butyl 1-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylateHCID 672510032-(2-(Bromomethyl)phenyl)-2H-1,2,3-triazole

Product 1

HCID 67253417tert-butyl 2-(2-(2H-1,2,3-triazol-2-yl)benzyl)-1-oxo-2,9-diazaspiro[5.5]-undecane-9-carboxylateYield 99%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

NaH (308 mg, 7.69 mmol, 60% in mineral oil) was added to an ice-cold solution of tert-butyl 1-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylate [1198284-94-4] (1.127 g, 4.08 mmol), 2-(2-(bromomethyl)phenyl)-2H-1,2,3-triazole (described separately as building block) (1.0 g, 4.16 mmol) and TBAI (78 mg, 0.208 mmol) in THF (30 mL). The resulting mixture was stirred at 0° C. for 1 h. The reaction mixture was allowed to warm to rt and stirred for 4 h. To the mixture water was added and the solution was extracted twice with ethyl acetate. The organic layer was washed with water and brine, filtered and dried over anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure. The product was purified by flash-column chromatography over silicagel (eluent: gradient 5%-65% ethyl acetate/heptane) to yield the title compound (1.77 g, 99%). [1H NMR (400 MHz, DMSO-d6) ♀ ppm 8.11 (s, 2H), 7.61-7.59 (m, 1H), 7.52-7.46 (m, 2H), 7.23 (d, 1H), 4.53 (s, 2H), 3.69-3.65 (m, 2H), 3.11-3.07 (m, 2H), 3.03 (br s, 2H), 1.86-1.72 (m, 6H), 1.45-1.40 (m, 2H), 1.38 (s, 9H); LCMS RtA=1.17, [M+H]+=426.4].

Workup

  1. temperatureto warm to rt
  2. stirringstirred for 4 h
  3. extractionthe solution was extracted twice with ethyl acetate
  4. washThe organic layer was washed with water and brine
  5. filtrationfiltered
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationThe organic layer was concentrated under reduced pressure
  8. customThe product was purified by flash-column chromatography over silicagel (eluent: gradient 5%-65% ethyl acetate/heptane)

Sources & evidence

ORD record
ord-7b1732bf507941bd853b395614f88582
Source dataset
uspto-grants-2013_09
Patent number
US08530648B2

Reaction notes

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